HSV-1 Vaccine Patented by David Davido (co-inventor on Theravax) and Morrison (ACAM529 inventor)

[OFMDH]

No we're not all screwed there are new potential vaccines discovered and then patented all the time........and yes you guys read that right........ David Davido is the co-inventor with Halford on RVx's licensed intellectual property, patent 8,802,109 aka Theravax/Profavax and he has since patented this new vaccine (KOS-NA) last year, with none other than Lynda Anne Morrison.  Who is Lynda Anne Morrison? She's the lady behind a little live vaccine in human clinical trials called ACAM-529 being investigated by the FDA and a big pharma vaccine company from France. She's the one who developed ACAM529 while at the Knipe Lab when she was at Harvard.

 Thus you have the inventor of ACAM-529 and co-inventor of Theravax working together and have patented a new vaccine called KOS-NA for HSV-1. The actual patent http://www.freepatentsonline.com/y2016/0000903.htm

Quote

A mutant HSV-1 (referred to herein as KOS-NA) was generated. KOS-NA contains novel mutations in the UL39 gene, which encodes for a protein that is a large subunit of ribonucleotide reductase (i.e., ICP6). These UL39 mutations were found to alter two amino acids in ICP6 (R950H and L393P) and are responsible for attenuation of KOS-NA in vivo, and resulted in diminished ICP6 protein levels. These novel UL39 mutations regulate the expression and/or stability of ICP6 and severely impact HSV-1 pathogenesis. Mutant HSV viruses containing these mutations appear to protect against HSV infection and can serve as therapeutic vaccines to help combat preexisting HSV infection in infected individuals.

Is it any good and compared to what?

Well this vaccine is similar to AuRx's attenuation of ICP10 so it ought to be similar. You see both ICP6 and ICP10 are really the same things with different names. They're just called different numbers because ICP6 is for HSV-1 and ICP10 is HSV-2, but they're both the ORF (open reading frame) called UL39. UL39 which makes a protein that contains a large subunit of ribonucleotide reductase and this RR is a major enzyme that the virus uses to eventually make all the new DNA for more viruses. In fact UL39 is so prolific its the dominant protein of HSV and it even helps drive the host's immune response away from suppressing the virus's replication. Here they tested prophylactic use and it was great....... As a sidenote Davido basically accidentally discovered this while working with ICP0, and just like Halford looked at a possible prophalaxtic vaccine (yes he accidentally discovered it: per https://link.springer.com/article/10.1007/s13365-016-0468-x - 

Quote

"Efforts to generate HSV-1 mutants in the infected cell protein 0 (ICP0) gene identified a mutant, KOS-NA that was severely impaired for acute replication in the eyes and TG of mice. Sequencing of the KOS-NA genome to identify the mutation(s) responsible for these impaired phenotypes revealed two non-synonymous mutations in the UL39 gene,"

Now is it any good as a therapeutic though? 

If you followed my Th1/Th2 posting you ought to be asking yourself right now, what is the Th1/Th2 ratio (and thus the type of antibodies being made) for this to quality as a good therapeutic? Well AuRX's patent recommended a ratio of at least 2.5 (even though her ICP10 mutant reached only 2.0). Sadly the patent for KOS-NA does not answer this, but the graphs do indicate a nice bump of CD4 cells expressing interferon were generated. Accordingly it ought to have a good Th1 response as INF-y, which suppresses replication ONLY comes from a Th1 immune response, not a type 2 one which we all have since we're obing. 

Conclusion

Another vaccine candidate specific for HSV-1 worthy enough that the inventors spent the cash to patent it. If the immune response is shifted much more to Th1 (IgG2a antibodies) as opposed to Th2 (and IgG1 antibodies) which appears possible because of the large INF-y bump in the graphs, this could be a worthy live vaccine to help suppress replication inside infected people as opposed to just being a prophylactic. 

[OFMDH]

Now what would be interesting is if RVx, since they're already licensing patent 8,802,109 from Davido and Halford go ahead and license KOS-NO (https://www.google.com/patents/US20160000903) once that application is done from Davido and Morrison and try that in St. Kitts.... I don't know if Morrison would agree to that though.... 

 

[useless]

Can you keep us all informed about this vaccine. I'msurprised not a lot of ppeopleoon here ggetting excited.  

[Seeker1960]

When will this get to human trials?

[impugn]

Hey @OhFuckMyDickHurts, you seem to be quite happy about this vaccine. Why would this be superior to what Halford is doing? This is definitely a curveball, you have the cofounder of Theravax coming out with his own vaccine. What does that say about RVx? 

[Disc0rdant]

Well.  This would be nice for my potential partners who are negative if it works and comes to market

[OFMDH]

1 hour ago, Seeker1960 said:

When will this get to human trials?

Its only a patent application, there is no business plan behind it or being announced. I do suggest though that RVx look at more than just Theravax, KOS-NO has potential for HSV1 sufferers and they're doing more trials. It would be great if more live vaccines are tried out. While not as attenuated in my opinion, it all has potential to advance the field. 

[OFMDH]

1 hour ago, impugn said:

Hey @OhFuckMyDickHurts, you seem to be quite happy about this vaccine. Why would this be superior to what Halford is doing? This is definitely a curveball, you have the cofounder of Theravax coming out with his own vaccine. What does that say about RVx? 

Softball anyone?

Happy? Basically its another potential vaccine, which is always great to advance the field. More search and more results. As for actually coming out, they're merely patenting it. No one says they have any money to run trials or are intending to license this to RVx to try out either. 

Superior? Theravax in Halford's 2015 publication showed about a number of slightly less than 1.0 for the ratio of 1gG2A to IgG1 non-neutralizing antibodies.  However when a third party in Maryland did it they got a ratio of 0.664. These antibodies correspond to Th1 vs Th2 type immune responses. A strong Th1 for infected people can means complete suppression of replication, whereas Th2 can enhance the disease.  It can do that because Th2 counteracts Th1 responses, so instead of stopping HSV, it helps stop the immune system from holding it back. All that malarkey about subunits not working is not necessarily true. The actual results showed in a recent study Jan 2017 of Theravax vs a DNA vaccine of gD2+Interleukin 12, they both worked as prophylactic vaccines in mice. That is because IL-12 drives a strong Th1 response, and thus it was able to suppress replication with the safety profile of a subunit vaccine.

Theravax is innovative in the sense that its a potential working Th2 dominant prophylactic vaccine which is counter intuitive as again mountains of data show Th1 actually suppresses replication. This is not a new concept though as it has already been shown to work in other diseases. However as a therapeutic vaccine it has a limited potential to only help a small segment of the population (in my opinion). 

As for KOS-NO this vaccine appears to be Th1 dominant as the patent shows a nice INF-Y response, and is attenuating by going against the dominant antigen ICP10 - this actually slows replication and weakens the virus. 

[OFMDH]

4 hours ago, useless said:

Can you keep us all informed about this vaccine. I'msurprised not a lot of ppeopleoon here ggetting excited.  

It's a patent application. I cannot find much more about it. Morrison appears to be keeping it under wraps for the most part. She has been focusing on chemotherapy aka antivirals for so long since she left Knipe's lab at Harvard and Davido has always been about ICP0 and still appears to be after what he and Halford thought of as the holy grail -  trying to figure out whether ICP0 causes the virus to switch from latency to reactivation. To me this is a pointless and moot task as microRNA's from LAT have been discovered and that with what is going inside the cell is what probably really causes it to switch from being latent to replicating. 

 

[OFMDH]

4 hours ago, useless said:

 ....... I'msurprised not a lot of ppeopleoon here ggetting excited.  

Lynda Morrison was willing to put her name on the patent and run experiments with it.. all great signs. Also since her prior vaccine ACAM529 was picked up by big pharma vaccine company this is the dawn of a potential successor. People ought to be a little excited - even if its years away from clinical trials, if ever. 

[dont quit!17]

I wonder if this means that ACAM 529 flopped during their phase 1 trial? But overall good news, the more research the better. 

[West end gal]

6 hours ago, useless said:

Can you keep us all informed about this vaccine. I'msurprised not a lot of ppeopleoon here ggetting excited.  

I am!

[Seeker1960]

Can get excited about a concept that may never be developed into a prototype and tested. Excited about the idea but it still has to get beyond that stage.

Can get excited about a concept that may never be developed into a prototype and tested. Excited about the idea but it still has to get beyond that stage.

[FutureRDH]

I would like to be a guine pig for this vaccine, I will definilike to be updated on this topic. Thanks! 

[hopeful Rylee]

It's only for HSV1?

[useless]

Why doesn't someone ask Halford to speak to David and Morrison about this since the two vaccines areso cclosely linked.